This is a proposal to establish laser microdissection instrumentation using Laser Microdissection and Pressure Catapulting (LMPC) technology at the University of Kentucky. Laser microdissection technology has become a standard for cutting-edge biomedical research at many institutions and clearly will revolutionize studies of gene and protein expression. Numerous NIH-supported projects at UK focus on gene and protein expression approaches, in many cases with a clear focus on particular cell types, tissue lesions, genetically modified loci, and even subcellular regions. The ability to incorporate computer-automated, highly selective specimen collection will vastly accelerate research progress, refine interpretation, and drive the discovery of novel mechanisms in various physiological and pathological conditions that are the focus of UK's research enterprise. In particular, major user projects at UK emphasize detection of subtle changes in tissue, cell, and subcellular compartments in various cell types, cancerous lesions, and plaques, with aging, Alzheimer's disease, inflammation, traumatic brain injury, oxidative stress, and infection and heavily integrate translational goals with the concept of personalized medicine. The integrated system proposed here (Zeiss PALM MicroBeam) has the power, accuracy, and flexibility to address the diverse needs of the Major Users in this application and will allow researchers to focus on homogenous cell collection derived from extant tissue. Coupled with the molecular expertise at UK, this system will allow our researchers to investigate the critical interplay among different cell types at the transcriptional and proteomic levels during pathological processes, leading to rational development of new drugs and individualized pathological diagnoses. Thus, the proposed system will not only specifically enhance progress in multiple NIH-funded projects at UK, but will facilitate the development of new methods that may well benefit investigators at many other institutions as well. Relevance: In recent years, advances in molecular measurement technology (e.g., proteomics, gene expression arrays) have yielded important insights into disease processes. The equipment proposed here will bring sampling technology (i.e., the ability to select an area of tissue for study at the cellular or even subcellular level) up to the same standard. The combination of advanced molecular analysis and cell-level collection specificity will allow us to investigate the roles of different kinds of cells in diseases such as Alzheimer's, cancer and heart disease, leading to rational development of new drugs and individualized medicine approaches for treatment.